Abstract

Introduction

Several studies reported an association between type 2 diabetes mellitus (DM2) and hepatocellular carcinoma (HCC). Data from several retrospective studies and meta-analysis have demonstrated a risk reduction of about 50% of developing HCC in cirrhotic patients treated with metformin for DM2. Several in vitro studies have shown anti-tumor activity of metformin (M) in HCC. The aim of this study is to evaluate the different outcomes of patients that have received or not metformin during treatment with sorafenib (S).

Methods

From 257 patients diagnosed with HCC from 2004 to 2014, 93 patients consecutively treated with sorafenib were analyzed. Of these, 42 patients (45.2%) were diabetic and 31 (33.3%) of these have received M for DM2. Progression-Free Survival (PFS), Overall Survival (OS) and their 95% Confidence Interval (95% CI) were estimated by Kaplan-Meier method and compared with log-rank test.

Results

The concomitant use of S and M was associated with a median PFS of 2.6 months (95% CI 1.9-3.3) compared to 5.0 months (95% CI 2.5-8.2) for patients who have not received M (p = 0.029). The concomitant use of S and M was associated with a median OS of 10.4 months (95% CI 3.9-14.4) compared to 15.1 months (95% CI 11.7-17.8) for patients who have not received M (p = 0.014).

Conclusion

These findings could be explained by an increased tumor aggressiveness and resistance to S in patients treated with M. M usually enhanced the activity of S, but probably molecular alterations in transporter genes or transcription factors involved in M molecular action and pharmacokinetics could contribute to a different response to these drugs combination. Further studies are needed to confirm the data and to identify possible mechanisms of resistance that may occur during treatment with S.